tbuckley/cabot-search huggingface dataset:
The ELiPSE-1 study: A phase 1, multicenter, open-label study of CNTY-101 in subjects with relapsed or refractory CD19-positive B-cell malignancies.
Authors: Krish Patel, Sarah Rothman, Poulomee A Das, Stephanie Yee, Indu Ramachandran, Iphigenia Koumenis, Terry A Cook, Ying Yuan, Nikolaus S. Trede, Ahmad Hatem Mattour
Journal: Journal of Clinical Oncology (2023)

TPS7580 Background: Century Therapeutics’ foundational technology is built on induced pluripotent stem cells, differentiated from allogeneic approaches that utilize non-renewable donor-derived cells. This approach allows production of a clonal cell bank of precisely edited cells that can be expanded and differentiated to supply large amounts of homogeneous allogeneic therapeutic products for off-the-shelf use. CNTY-101 is an allogeneic Chimeric Antigen Receptor NK (CAR-NK) cell product with genetic modifications designed to specifically target CD19-expressing B-cell malignancies, reduce allorejection in the recipient allowing for repeat dosing, increase persistence, and enable cell elimination in the event of unexpected adverse events. CNTY-101, as a CAR-NK product, has the potential for improved safety over T-cell based cellular therapies. Methods: This first-in-human study will determine the MTD and recommended Phase 2 regimen (RP2R) of CNTY-101 in combination with subcutaneous (SC) IL-2 in patients with R/R aggressive and indolent CD19-positive B-cell Non-Hodgkin lymphomas including diffuse large B-cell lymphoma, mantle cell lymphoma, primary mediastinal large B-cell lymphoma, follicular lymphoma and marginal zone lymphoma, who are without other treatment options. Part 1 of the study (dose escalation using the BOIN design) will start with a dose of CNTY-101 cells without IL-2 (1 to 3 subjects), followed by dose escalation up to four dose cohorts administering a single dose of CNTY-101 cells in combination with IL-2 daily for 8 days (Sched A). After the single-dose MTD (or the maximal single dose) has been reached, a fractionated schedule of 3 doses per 28-day cycle, administered on Days 1, 8, and 15 (Sched B), will also be explored, starting with approximately one-third the maximum single dose level of CNTY-101, followed by escalation/de-escalation. Subjects in whom CNTY-101 shows signs of clinical benefit (i.e. stable disease or better per Lugano 2014 criteria) may receive additional cycles of CNTY-101 if the Investigator, Sponsor, and appropriate regulatory authorities, as required, concur that the benefit-risk is positive. One overall CNTY-101 RP2R will be declared in Part 1. Part 2, expansion, will further evaluate the safety, pharmacokinetics (PK), and efficacy of the CNTY-101 regimen, treating up to an additional 12 subjects to reach a total of approximately 20 subjects treated at the RP2R. In addition to safety and efficacy endpoints, the trial will evaluate exploratory PK, immunogenicity and pharmacodynamic endpoints including evaluations of tumor cfDNA, iNK tumor trafficking and serum cytokines. Clinical trial information: NCT05336409 .
Multi-institutional study evaluating the role of circulating tumor DNA (ctDNA) in management of appendiceal cancers (AC).
Authors: Erika Belmont, Varun Vivek Bansal, Mohammad A. A. Zeineddine, Michael White, Blase N. Polite, Chih-Yi Liao, Oliver S. Eng, Kiran Turaga, John Paul Y.C. Shen, Ardaman Shergill
Journal: Journal of Clinical Oncology (2023)

4170 Background: AC frequently present with peritoneal metastases (PM) which are difficult to accurately measure with imaging techniques or serum tumor markers. ctDNA is a novel, promising biomarker to assess minimal residual disease (MRD) and therapy response. Its utility in AC with PM is poorly studied due to the rarity of this disease condition. This is a report on the role of ctDNA in AC management. Methods: Patients with AC managed at two high volume centers between 01/01/2019 to 12/15/2022were included in this study. CtDNA measurements were prospectively collected using Signatera tumor informed ctDNA assay during clinical care and these data were abstracted retrospectively. Cox-proportional hazards were utilized for survival analysis. Results: 97 patients with AC were included with a median age of 57 (IQR 53-66) years, majority being non-Hispanic white (85%) and female (63%). 68 (70%) patients had ctDNA assay drawn at the time of confirmed clinical disease (radiographic or laparoscopic). The sensitivity of ctDNA was 56% (CI 44% - 67%)) for all grades, and 66% (CI 49% - 80%) for grade 3 tumors. 65 (67%) patients underwent cytoreductive surgery (CRS), of which 16 (24.6%) had preoperative ctDNA assays. Sensitivity in this cohort of surgical patients was 25% and positive ctDNA showed poor correlation with PCI score at time of surgery (n=4, r = 0.38, p = 0.14). Any positive value for post-operative ctDNA was associated with lower disease free survival (DFS) (9 months (CI 5-13) in low grade AC and 10 months (CI 7-14) in high grade AC, compared to not reached for those persistently negative (p&lt;0.001) over a median follow-up duration of 17 months. This difference persisted despite adjusting for adjuvant chemotherapy for high-grade disease (aHR = 11.2 (1.4-88.6), p = 0.023). Conclusions: This is the largest study reported to date of tumor informed ctDNA testing in patients with AC. These data show that ctDNA has low sensitivity in both the metastatic unresectable and in pre-operative settings. However, ctDNA positivity after CRS in AC has prognostic value and could be used to guide systemic therapy decisions.
Rapid establishment of patient-derived organoids from treatment-naive head and neck cancer patients for drug and radiosensitivity screening.
Authors: Inge Tinhofer, Anne-Sophie Fisch, Ana Pestana, Christian Doll, Max Heiland, Steffen Dommerich, Theresa Obermüller, Veit Maria Hofmann, Konrad Friedrich Klinghammer, Iris Piwonski, Simon Schallenberg, Daniel Zips
Journal: Journal of Clinical Oncology (2023)

e18043 Background: Patient-derived organoids (PDOs) have been shown to be powerful tools for modeling disease and patient-individualized drug sensitivity screening, opening a novel avenue to precision medicine. A major challenge for guidance of clinical decisions is the extended time frame for establishing these models. Here, we report the feasibility of a refined protocol for PDO generation from head neck squamous cell carcinoma (HNSCC) tumors, suitable to guide personalized treatment decisions in the curative setting. Methods: After informed consent, tumor tissue specimens from 145 newly diagnosed HNSCC patients were collected during diagnostic biopsy or curative surgery. Following mechanic / enzymatic dissociation and initial expansion in 2D cultures, tumor cells were seeded in extracellular matrix (Matrigel) to form PDOs. Primary endpoint of the study was the PDO engraftment rate. In additio, the time needed for ex vivo expansion of PDO cultures for personalized drug/radiosensitivity testing was determined. Interference of patient and tumor characteristics with PDO engraftment was analyzed using SPSS version 27. Results: The PDO engraftment rate in the entire cohort was 51% (n = 74 of 145 patients). Neither tumor stage, grading, anatomical sublocalisation, HPV status nor sample type (biopsy vs. surgical specimen) were significantly associated with PDO establishment. Of note, Kaplan-Meier analysis revealed a trend between successful ex vivo engraftment and reduced overall survival (log-rank: p = 0.09), suggesting preferential engraftment of aggressive poor prognosis tumors. Engraftment rate in the subgroup of patients with recommendation for adjuvant chemoradiation was 58%. Time for expansion of PDO cultures for subsequent drug/radiation screening was 18.5 ± 9.6 days (median ± SD). Expansion was completed before start of adjuvant chemoradiation in all but one cases. Conclusions: Our study suggests feasibility of PDO generation for locally advanced aggressive HNSCC within a timeframe suitable for guiding treatment decisions for adjuvant therapy. Planned future directions include clinical validation of drug testing results for individual patients and clinical study cohorts.
A radiomics model developed from pre-metastatic brain magnetic resonance imaging to predict brain metastasis in non–small-cell lung cancer: Evidence to the seed-and-soil theory.
Authors: Xiao Chu, Jing Gong, Zhengfei Zhu
Journal: Journal of Clinical Oncology (2023)

2030 Background: Steven Paget’s “seed and soil” theory suggests that both the primary tumor and the target host organ play important roles in successful metastasis development. In this proof-of-concept study, we proposed that inter-individual differences exist in the brain’s congeniality for developing brain metastasis (BM), and validated the theory via developing a non-invasive radiomics BM prediction model. Methods: 256 non-small cell lung cancer (NSCLC) patients with no BM at baseline brain magnetic resonance imaging (MRI) were selected, 128 patients developed BM within three years after diagnosis and 128 remained BM-free. For radiomics analysis, both the BM and non-BM groups were randomly distributed into training and testing datasets at an 70%:30% ratio. Baseline brain MRI (representing the soil) and chest computed tomography (CT, representing the seed) radiomics features were extracted to develop the BM prediction models. We first developed radiomics models using the training dataset and subsequently validated the models in the testing dataset. A radiomics BM score (RadBM score) was generated and BM-free survival were compared between RadBM score-high and RadBM score-low groups. Results: The radiomics model developed from baseline brain MRI features alone can predict BM development in NSCLC patients. Furthermore, a fusion model integrating brain MRI features with primary tumor CT features (seed-and-soil model) provided synergetic effect and was more efficient in predicting BM (areas under the receiver operating characteristic curve 0.84[95% confidence interval: 0.80–0.89] and 0.80 [95% confidence interval: 0.71–0.88] in the training and testing datasets, respectively). BM-free survival was significantly shorter in the RadBM score-high group versus the RadBM score-low group (Log-rank P &lt; 0.001). Cumulative BM rate at 3-year were 75.8% and 24.2% for RadBM score-high and RadBM score-low group, respectively. Conclusions: The results demonstrated that intrinsic features of a non-metastatic organ exert a significant impact on metastasis development, which is first-in-class in metastasis prediction studies and provided novel evidence for the "seed-and-soil" theory of tumor metastasis. Radiomics BM prediction model utilizing both pre-metastatic brain and primary tumor features might provide a useful tool for identifying NSCLC patients more prone to develop BM and providing individualized management for these patients.
Diagnostic and prognostic biomarker value of blood circulating inflammatory cytokines in hepatocellular carcinoma.
Authors: Shadi Chamseddine, Ahmed Omar Kaseb
Journal: Journal of Clinical Oncology (2023)

e16115 Background: Circulating inflammatory cytokines play critical roles in tumor-associated inflammation and immune responses. Recent data has suggested that several interleukins (ILs) mediate carcinogenesis in hepatocellular carcinoma (HCC). However, the predictive and prognostic value of circulating ILs has yet to be validated. Our study aimed to evaluate the association of the serum ILs with overall survival (OS) and clinicopathologic features in a large cohort of HCC patients. Methods: We prospectively collected data, and serum samples from 767 HCC patients treated at The University of Texas MD Anderson Cancer Center between 2001 and 2014, with a median follow-up of 67.4 months (95% CI: 52.5, 83.3). Biomarker association with overall survival (OS) was evaluated by the Log-rank method. Results: The median OS in this cohort was 14.2 months (95% confidence interval [CI]: 12, 16.1 months). Clinicopathologic features were more advanced, and OS was significantly inferior in patients with high circulating levels of IL1-R1, IL-6, IL-8, IL-10, IL-15, IL-16, and IL-18. Conclusions: In conclusion, our study shows that several serum IL levels are valid prognostic biomarker candidates and potential targets for therapy in HCC.
Predicting absolute benefit in risk of metastasis of androgen deprivation therapy added to radiation therapy in patients with newly diagnosed prostate cancer using Prolaris.
Authors: Jonathan David Tward, Lauren Lenz, Alexander Gutin, Wyatt Clegg, Rob Finch, Todd Cohen
Journal: Journal of Clinical Oncology (2023)

5030 Background: Most patients would defer using androgen deprivation therapy (ADT) with radiation therapy (RT) when the number-needed-to-treat (NNT) exceeds 25 persons to prevent 1 from developing metastasis, corresponding to an absolute benefit of 4%. 1 However, no tools for estimating personalized NNT or absolute benefit from ADT exist. We aimed to quantify personalized absolute benefit and NNT for persons receiving ADT added to single modality RT. Methods: The clinical cell-cycle risk (CCR) score combines the University of California, San Francisco’s Cancer of the Prostate Risk Assessment and the cell cycle progression molecular score to accurately assess prostate cancer aggressiveness. The effect of ADT added to RT was modeled using a 10-year risk of metastasis as a function of continuous CCR score for patients treated with RT alone. The relative benefit of ADT added to RT to reduce distant metastasis was modeled using published data from The Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) which utilized several prospectively randomized RT±ADT trials. 2 The average absolute benefit was calculated for patients with CCR scores above and below a prespecified multimodality treatment threshold (MTT) using the distribution of scores in a cohort of patients commercially tested by Myriad Genetics. Results: The commercially tested cohort consisted of 56,485 patients spanning all National Comprehensive Cancer Network risk categories (33.7% very low/low risk, 29.8% favorable intermediate risk, 25.6% unfavorable intermediate risk, 11.0% high/very high risk), with 87.2% having CCR scores at or below the MTT and 12.7% with CCR scores above the threshold. The average absolute benefit of ADT treatment was 0.86% (NNT=116) for patients with CCR scores below the MTT and 8.2% (NNT=12) for patients with CCR scores above the MTT. Patients with CCR scores at precisely the MTT had a predicted absolute benefit of 3.7% (NNT=27). Conclusions: The Prolaris test can accurately predict an individual's benefit of adding ADT to RT, and the risk threshold is consistent with patient attitudes about when to use or omit ADT. 1. Spratt DE, Tward JD: IJROBP 108:899-902, 2020. 2. Kishan AU, Sun Y, Hartman H, et al. Lancet Oncol 23:304-316, 2022.
Predictive value of tumor-infiltrating lymphocyte (TIL) dynamics in the tumor microenvironment (TME) during preoperative chemoradiotherapy (CRT) on pathologic complete response (pCR) in microsatellite-stable (MSS) locally advanced rectal cancer (LARC).
Authors: Mitsuho Imai, Hideaki Bando, Yuichiro Tsukada, Takeshi Kato, Yoshito Komatsu, Mamoru Uemura, Satoshi Yuki, Akinobu Taketomi, Takao Fujisawa, Yoshiaki Nakamura, Motohiro Kojima, Shohei Koyama, Chiyoon Oum, Seunghwan Shin, Chan-Young Ock, Hiroyoshi Nishikawa, Masaaki Ito, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2023)

3608 Background: Preoperative CRT followed by consolidation nivolumab before surgery showed a promising pCR rate in MSS LARC; both high PD-L1 expression and an elevated CD8 + T cell/effector regulatory T cell ratio analyzed by pre-CRT samples were independently related to high pCR rate (Bando H, Clin Cancer Res. 2022). Here, we applied AI-powered spatial TIL analysis to the VOLTAGE study to investigate whether dynamic change of TIL in TME may predict pCR in MSS LARC. Methods: The VOLTAGE study is a multicenter phase I/II study to evaluate the efficacy of CRT followed by 5 cycles of nivolumab and surgery in patients (pts) with LARC. In this study, tumor samples were obtained at multiple time points; pre-CRT (B1), post-CRT/pre-nivolumab (B2), post-3 cycles of nivolumab (B3), and surgery. In this analysis, a total of 86 H&amp;E whole-slide images (WSI) harvested at B1 and B2 time points from all the pts enrolled in the VOLTAGE study were included in the analysis. Lunit SCOPE IO (Lunit, Republic of Korea), AI-powered H&amp;E-WSI analyzer developed based on 16,443 WSI with pathologists' annotations, was applied to quantify TIL density in TME. Results: In a total of 43 pts, pCR rate of MSS and microsatellite instability-high (MSI-H) were 28.9% (11/38) and 60% (3/5), respectively. In MSS subgroup (n = 38), which has a higher unmet need for pCR prediction, tumor samples with pCR (n = 11) had increased TIL density in TME (tTIL) in post-CRT (B2, median [IQR] 726 [249-1607] /mm 2 ) compared to pre-CRT (B1, 598 [366-905] /mm 2 ), whereas those without pCR (n = 27) had decreased tTIL in post-CRT (405 [148-748] /mm 2 ), compared to pre-CRT (B1, 748 [460-1153] /mm 2 ). Intratumoral TIL density changes were more prominent than stromal TIL density changes in MSS tumor samples with pCR (mean fold change x17.7 vs. x1.5). MSS Pts with tTIL change from B1 to B2 (during CRT) more than x1.8 times achieved 75% (6/8) pCR rate, whereas those with tTIL change less than x1.8 had 16.7% (5/30) pCR rate (p = 0.0035). Conclusions: Change of TIL density in TME during CRT was significantly correlated with favorable clinical outcome of preoperative CRT and consolidation nivolumab, resulting in high pCR rate in MSS LARC.
Efficacy and safety of ponatinib in management of chronic myeloid leukaemia: Experience from Kenya.
Authors: Nicolas Anthony Othieno-Abinya, Angela Awino Mcligeyo, Peter Omondi Oyiro, Andrew Oluoch Odhiambo, Mohammed Shabbir Ezzi, Sitna Ali Mwanzi, Mary Flaviane Nyangasi, Matilda Ong'ondi, Walter Mwanda, Valerian Mwenda, Miriam Claire Mutebi
Journal: Journal of Clinical Oncology (2023)

e19067 Background: BCR-ABL tyrosine kinase inhibitors imatinib, nilotinib, bosutinib, and dasatinib, are used upfront in the management of chronic myeloid leukaemia (CML). In terms of resistance, ponatinib is the most potent tyrosine kinase inhibitor used in CML. It is however not used as first line therapy because of the fear of cardiovascular toxicity. However, because of a lot of inconsistency in the way oncology and cardiovascular trials define adverse events, this risk is not well defined. Methods: To document the efficacy and safety of ponatinib among CML patients treated at the Max Access Solutions Clinic at the Nairobi Hospital retrospectively. Results: Fourty-five patients were included between 02-10-2017 and 03-12-2022; males 23(51.1%) and females 22 (48.9%). All patients took imatinib first line. Ponatinib was taken second line by 10 (22.2%), third line by 18 (40%) and 4 th line by 17 (37.8%). Of these, 25 (55.6%) were in chronic phase, 10(22.2%) accelerated and 9(20%) blastic phases. Of 22 evaluable cases in chronic phase, 1 (4.5%) died after 9 months on ponatinib, the rest are on follow-up for 1 – 60 months with a mean of 16.8 months and median of 10 months. Of 8 evaluable in accelerated phase, one (12.5%) died after 36 months. The range of follow-up is 2-36 months and mean 19.4 months. Of 9 evaluable in blastic phase, two (22.2%) are still alive after 6 and 41 months respectively. Seven (77.8%) died after follow-up ranging from 2-18 months, mean of 9.3 months. Interquartile range (IQR) for total white blood cell (wbc) count dropped from 9.08 x 10 9 /litre to 4.82 x 10 9 /litre on ponatinib, absolute neutrophil count dropped from 6.70 x 10 9 /litre to 2.29 x 10 9 /litre and platelets IQR rose from 114 x 10 9 /litre -163 x 10 9 /litre. Adverse events were registered in 6 (13.3 %), mainly grade 1-2, none of which was cardiovascular. Conclusions: Ponatinib is an active in all phases of CML with manageable side effect profile.
Laparoscopic versus open-surgery in FIGO stage II endometrioid endometrium cancers: Is there a prognostic effect?
Authors: Daniel Uwe Reimer, Tanu Priya Bargujar, Katharina Leitner, Katharina Steger, Thomas Bartl, Christian Marth, Alain G Zeimet
Journal: Journal of Clinical Oncology (2023)

5605 Background: Based on two randomized trials (LACE and LAP2) minimal invasive surgery has turned into the surgical standard in early stage endometrial cancer including “high-risk” patients. However, these recommendations are predominately based on “low-risk” cancers, which are mainly represented in both trial collectives. We herein provide a retrospective study, which focuses on potential differences in clinical outcome in early stage endometrioid endometrial cancers with distinct risk constellations treated by laparoscopy or open surgery. Methods: 420 early stage endometrial cancers were retrospectively dichotomized according to the surgical approach and correlated to the recurrence rate and clinical outcome. In addition, subgroup analyses were performed according relevant clinical risk parameters, namely FIGO stage, grading and LVSI. Results: The analyzed collective consisted of 73.8% stage IA, 19.5% stage IB, and 6.7% stage II cases. Twenty-tree percent of patients exhibit G3 tumors and LVSI was detected in 12.4%. Minimal invasive surgery was performed in 54.5% of study patients. During a median follow-up of 5.0 years, recurrence or death were observed in 8.3% and 6.7%, respectively. Recurrences were predominately located in the vaginal cuff (n = 21; 60.0%), to a minor extent in loco-regional lymph nodes (n = 11; 31.4%), and in three patients (8.6%) in both sides. No distant metastases were detected at first recurrence. Also under consideration of the mentioned clinicopathologic parameters, the surgical approach in FIGO stage I did not influence the recurrence rate and patients’ survival. However, in a subgroup analysis of stage II disease, the laparoscopic approach was clearly associated with a significant higher recurrence rate (85.7% vs. 14.3%; p = 0.013). All of the recurrences were located in the vaginal cuff, and in one case, additional relapse was found in loco-regional lymph nodes. Moreover, laparoscopic surgery in stage II disease was associated with impaired progression-free and overall survival (HR 8.86 (1.008 – 20.85) and HR 6.36 (1.102 – 28.61), respectively). Conclusions: We herein demonstrate that a minimal invasive surgical approach in stage II endometrial cancer is associated with higher recurrence rates and impaired clinical outcome. These data could be interpreted to be in line with the results of the LACC trial in cervical cancer. Although, grounded on a retrospective analysis, these hypothesis-generating results warrants a confirmatory trial, which is ongoing in a much larger collective of stage II endometrial cancer patients.